Males and females differ profoundly at virtually all levels of biological organization, from morphology and behavior to gene expression and disease risk. A key force that molds these differences is sexually antagonistic selection, in which a gene that is beneficial in one sex is detrimental in the other. This type of selection is thought to drive the evolution of several features of the genome, and it has also been hypothesized to underlie sex-specific differences in disease susceptibility in humans. Despite its importance, we have little direct information about where sexually antagonistic selection acts in the genome or about its role in creating differences between the sexes. Sex chromosomes are the most promising context in which to study sexually antagonistic selection because they are predicted to be hotspots for the accumulation of genes experiencing this type of selection. Furthermore, sexually antagonistic selection is thought to be responsible for the evolution of the distinctive properties of sex chromosomes, such as a reduction in recombination between the X and the Y, and the subsequent degeneration of the Y. Much of the existing data from sex chromosomes, however, comes from systems with sex chromosomes that are highly degenerate and gene-poor, rendering the identification of genes experiencing sexually antagonistic selection difficult or impossible. Stickleback fishes are an emerging model system whose sex chromosomes still recombine and are gene-rich, making them ideally suited for studying sexually antagonistic selection. This research project will exploit those properties to learn how sexually antagonistic selection sculpts chromosomes, genes, and phenotypes. The three major aims will: (1) use genetic, cytogenetic, and genomic tools to reveal how recombination between the X and Y chromosomes becomes suppressed; (2) obtain whole genome sequences to study how the many differences between males and females alter the evolutionary trajectories of genes and chromosomes; and (3) use new statistical methods to identify the genetic and phenotypic targets of sexually antagonistic selection. The results from this project will be useful in context far beyond sex chromosomes in sticklebacks. It will generate technical innovations, such as new statistical methods for analyzing DNA variation that will be valuable for studies of chromosomal rearrangements on autosomes in diverse taxa. Furthermore, insights from this work will provide perspectives on the potential for selection to establish genes that are detrimental to health in al species, including humans.